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Synonyms | NSC 122750 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C29H40N2O9 |
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分子量 | 560.64 | CAS No. | 30562-34-6 | |
Solubility (25°C)* | 体外 | DMSO | 36 mg/mL warmed with 50ºC water bath (64.21 mM) | |
Water | Insoluble | |||
Ethanol | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | Geldanamycin is a natural existing HSP90 inhibitor with Kd of 1.2 μM, specifically disrupts glucocorticoid receptor (GR)/HSP association. Geldanamycin attenuates virus infection-induced ALI (acute lung injury)/ARDS (acute respiratory distress syndrome) by reducing the host's inflammatory responses. |
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in vitro | Geldanamycin binds in the ATP-binding site in the N-terminus domain of Hsp90s (residues 1-220). Geldanamycin inhibits the ATPase activity of Hsp90 in a dose-dependent manner. [1] Geldanamycin causes a dose-dependent G2 arrest and reversible inhibiton o f entry into the S phase in A2780 human ovarian cell line. This inhibition is accompanied by p53 increase and finally demonstrated to be p53 dependent. [2] Geldanamycin causes polyubiquitination and proteasomal degradation of the p185 receptor protein-tyrosin kinase and shows a IC50 with 70 nM. [3, 4] Geldanamycin is a typical anti-tumor reagent, shows a mean GI50 with 0.18 μM against the panel of 60 human tumor cell lines. [5] |
in vivo | Geldanamycin (50 mg//kg) shows 30% inhibition on pl85-associated phosphotyrosine levels in FRE/erbB-2 mice. [6] |
キナーゼアッセイ | Isothermal Titration Calorimetry (ITC) of Nucelotide Binding | |
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The titration experiments are performed using the MSC system. In each experiment, 16 aliquots of 15 μL of geldanamycin (300 μM in 1% DMSO) are injected into 1.3 mL of protein (31 μM in 20 mMTris-HCl, pH 7.5, 1 mMEDTA) at 25 °C, and the resulting data are fit after subtracting the heats of dilution. Heats of dilution are determined in separate experiments from addition of geldanamycin into buffer and buffer into protein. No evidence for binding of DMSO in the nucleotide binding site is observed. Titration data are fit using a nonlinear least-squares curve-fitting algorithm with three floating variables: stoichiometry, binding constant (Kb) 1/Kd), and change of enthalpy of interaction (ΔH°). Dissociation constants estimated for geldanamycin binding to intact yeast Hsp90 is 1.22 μM, and for binding to Hsp90 N-terminal domain is 0.78 μM. No meaningful heat is observed with binding to the C-terminal fragment. | ||
細胞アッセイ | 細胞株 | A2780 human ovarian cell line |
濃度 | 0.001-10 μM | |
反応時間 | 3 hours | |
実験の流れ | Exponentially growing cells are treated with Geldanamycin and at various times DNA synthesis is assessed by incorporation of bromodeoxyuridine (BrdUrd) and flow cytometric analysis. No marked difference in total cell number is noted during this time course for treated and untreated cultures. BrdUrd (10 μM) is incorporated over a 4-h incubation period at 37 °C and cells are harvested and fixed in 70% ethanol. After denaturation of the DNA with 2 N HC1, cells are incubated with an anti-BrdUrd mouse monoclonal antibody followed by a fluorescein isothiocyanate (FITC)-linked goat anti-mouse IgG. Cells are stained for 30 minutes at room temperature with propidium iodide and analysed by flow cytometry using a Coulter EPICS Profile Analyzer. |
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動物実験 | 動物モデル | FRE/erbB-2 tumors in nu/nu mice |
投薬量 | 50 mg/kg | |
投与方法 | Administered via i.p. |
Data from [Data independently produced by , , Antimicrob Agents Chemother, 2015, 10.1128/AAC.00946-15]
Data from [Data independently produced by , , PLoS One, 2015, 10(9):e0138936.]
Data from [Data independently produced by , , Radiat Res, 2018, 189(5):519-528]
Inhibition of HSP90 in Driver Oncogene-Defined Lung Adenocarcinoma Cell Lines: Key Proteins Underpinning Therapeutic Efficacy [ Int J Mol Sci, 2023, 24(18)13830] | PubMed: 37762133 |
Development of a First-in-Class Small-Molecule Inhibitor of the C-Terminal Hsp90 Dimerization [ ACS Cent Sci, 2022, 8(5):636-655] | PubMed: 35647282 |
Local Elimination of Senescent Cells Promotes Bone Defect Repair during Aging [ ACS Appl Mater Interfaces, 2022, 10.1021/acsami.1c22138] | PubMed: 35014784 |
Proteome-Wide Deconvolution of Drug Targets and Binding Sites by Lysine Reactivity Profiling [ Anal Chem, 2022, 10.1021/acs.analchem.1c05455] | PubMed: 35147412 |
Hsp90 Regulates GCRV-II Proliferation by Interacting with VP35 as Its Receptor and Chaperone [ J Virol, 2022, 96(19):e0117522] | PubMed: 36102647 |
Hsp90 Regulates GCRV-II Proliferation by Interacting with VP35 as Its Receptor and Chaperone [ Journal of Virology, 2022, Vol. 96, No. 19] | PubMed: None |
Evolution of kinase polypharmacology across HSP90 drug discovery [ Cell Chem Biol, 2021, S2451-9456(21)00221-X] | PubMed: 34077750 |
Antibody-drug conjugate and free geldanamycin combination therapy enhances anti-cancer efficacy [ Int J Pharm, 2021, 610:121272] | PubMed: 34763035 |
Hsp90 is required for snakehead vesiculovirus replication via stabilizing the viral L protein [ J Virol, 2021, JVI0059421] | PubMed: 34037421 |
Solvent-Induced Protein Precipitation for Drug Target Discovery on the Proteomic Scale [ Anal Chem, 2020, 92(1):1363-1371] | PubMed: 31794197 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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